Surveillance in easy to access population subgroups as a tool for evaluating malaria control progress: A systematic review.

BACKGROUND: The need for surveillance systems generating targeted, data-driven, responsive control efforts to accelerate and sustain malaria transmission reduction has been emphasized by programme managers, policy makers and scientists. Surveillance using easy-to-access population subgroups (EAGs) may result in considerable cost saving compared to household surveys as the identification and selection of individuals to be surveyed is simplified, fewer personnel are needed, and logistics are simpler. We reviewed available literature on the validation of estimates of key indicators of malaria control progress derived from EAGs, and describe the options to deal with the context specific bias that may occur. METHODS: A literature search was conducted of all documents reporting validation of estimates of malaria control indicators from EAG surveys before the 31st of December 2016. Additional records were identified through cross-reference from selected records, other applicable policy documents and grey literature. After removal of duplicates, 13, 180 abstracts were evaluated and 2,653 eligible abstracts were identified mentioning surveillance in EAGs, of which 29 full text articles were selected for detailed review. The nine articles selected for systematic review compared estimates from health facility and school surveys with those of a contemporaneous sample of the same population in the same geographic area. RESULTS: Review of the available literature on EAGs suitable for surveillance of malaria control progress revealed that little effort has been made to explore the potential approach and settings for use of EAGs; and that there was wide variation in the precision of estimates of control progress between and within studies, particularly for estimates of control intervention coverage. Only one of the studies evaluated the geospatial representativeness of EAG samples, or carried out geospatial analyses to assess or control for lack of geospatial representativeness. Two studies attempted to measure the degree of bias or improve the precision of estimates by controlling for bias in a multivariate analysis; and this was only successful in one study. The observed variability in accuracy of estimates is likely to be caused by selection and/or information bias due to the inherent nature of EAGs. The reviewed studies provided insight into the design and analytical approaches that could be used to limit bias. CONCLUSION: The utility EAGs for routine surveillance of progress in malaria control at the district or sub-district programmatic level will be driven by several factors including whether serial point estimates to measure transmission reduction or more precise geospatial distribution to track 'hot-spots' is required, the acceptable degree of precision, the target population, and the resources available for surveillance. The opportunities offered by novel geostatistical analyses and hybrid sampling frames to overcome bias justify a renewed exploration of use of EAGs for malaria monitoring and evaluation.

Lack of decline in childhood malaria, Malawi, 2001-2010.

In some areas of Africa, health facility data have indicated declines in malaria that might have resulted from increasingly effective control programs. Most such reports have been from countries where malaria transmission is highly seasonal or of modest intensity. In Malawi, perennial malaria transmission is intense, and malaria control measures have been scaled up during the past decade. We examined health facility data for children seen as outpatients and parasitemia-positive children hospitalized with cerebral malaria in a large national hospital. The proportion of Plasmodium falciparum-positive slides among febrile children at the hospital declined early in the decade, but no further reductions were observed after 2005. The number of admissions for cerebral malaria did not differ significantly by year. Continued surveillance for malaria is needed to evaluate the effects of the increased malaria control efforts.

Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial.

BACKGROUND: There is a need for new artemisinin-based combination therapies that are convenient, effective, and safe. We compared the efficacy and safety of pyronaridine-artesunate with that of artemether-lumefantrine for treatment of uncomplicated P falciparum malaria. METHODS: This phase 3, parallel-group, double-blind, randomised, non-inferiority trial was undertaken in seven sites in Africa and three sites in southeast Asia. In a double-dummy design, patients aged 3-60 years with uncomplicated P falciparum malaria were randomly assigned in a 2:1 ratio to receive pyronaridine-artesunate once a day or artemether-lumefantrine twice a day, orally for 3 days, plus respective placebo. Randomisation was done by computer-generated randomisation sequence in blocks of nine by study centre. Intervention tablets contained 180 mg pyronaridine and 60 mg artesunate; control tablets contained 20 mg artemether and 120 mg lumefantrine. Both treatments were given according to bodyweight. The primary efficacy outcome was PCR-corrected adequate clinical and parasitological response (ACPR) rate at day 28 in the per-protocol population. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference between groups was greater than -5%. This study is registered with ClinicalTrials.gov, number NCT00422084. FINDINGS: 1272 patients were randomly assigned to treatment (pyronaridine-artesunate, n=849; artemether-lumefantrine, n=423). The per-protocol population consisted of 784 patients in the pyronaridine-artesunate group and 386 patients in the artemether-lumefantrine group. PCR-corrected ACPR rate at day 28 was 99.5% (780 patients; 95% CI 98.7-99.9) in the pyronaridine-artesunate group and 99.2% (383 patients; 95% CI 97.7-99.8) in the artemether-lumefantrine group (treatment difference 0.3%, 95% CI -0.7 to 1.8; p=0.578). There were 509 (60.0%) adverse events in 849 patients assigned to pyronaridine-artesunate and 241 (57.0%) in 423 patients assigned to artemether-lumefantrine. The most frequent drug-related adverse event was eosinophilia (pyronaridine-artesunate, 53 events [6.2%]; artemether-lumefantrine 24 events [5.7%]). 21 (2.5%) patients in the pyronaridine-artesunate group and seven (1.7%) in the artemether-lumefantrine group discontinued study drugs or were withdrawn from the study. Mild and transient increases in alanine aminotransferase and aspartate aminotransferase concentrations were seen in the pyronaridine-artesunate group but not in the artemether-lumefantrine group. INTERPRETATION: Efficacy of pyronaridine-artesunate was non-inferior to that of artemether-lumefantrine for treatment of uncomplicated falciparum malaria. Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes. FUNDING: Shin Poong Pharmaceutical and the Medicines for Malaria Venture.

Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysis.

BACKGROUND: Malaria is a major cause of morbidity and mortality in Africa. International effort and funding for control has been stepped up, with substantial increases from 2003 in the delivery of malaria interventions to pregnant women and children younger than 5 years in The Gambia. We investigated the changes in malaria indices in this country, and the causes and public-health significance of these changes. METHODS: We undertook a retrospective analysis of original records to establish numbers and proportions of malaria inpatients, deaths, and blood-slide examinations at one hospital over 9 years (January, 1999-December, 2007), and at four health facilities in three different administrative regions over 7 years (January, 2001-December, 2007). We obtained additional data from single sites for haemoglobin concentrations in paediatric admissions and for age distribution of malaria admissions. FINDINGS: From 2003 to 2007, at four sites with complete slide examination records, the proportions of malaria-positive slides decreased by 82% (3397/10861 in 2003 to 337/6142 in 2007), 85% (137/1259 to 6/368), 73% (3664/16932 to 666/11333), and 50% (1206/3304 to 336/1853). At three sites with complete admission records, the proportions of malaria admissions fell by 74% (435/2530 to 69/1531), 69% (797/2824 to 89/1032), and 27% (2204/4056 to 496/1251). Proportions of deaths attributed to malaria in two hospitals decreased by 100% (seven of 115 in 2003 to none of 117 in 2007) and 90% (22/122 in 2003 to one of 58 in 2007). Since 2004, mean haemoglobin concentrations for all-cause admissions increased by 12 g/L (85 g/L in 2000-04 to 97 g/L in 2005-07), and mean age of paediatric malaria admissions increased from 3.9 years (95% CI 3.7-4.0) to 5.6 years (5.0-6.2). INTERPRETATION: A large proportion of the malaria burden has been alleviated in The Gambia. Our results encourage consideration of a policy to eliminate malaria as a public-health problem, while emphasising the importance of accurate and continuous surveillance.